The present invention is in the field of enzyme proteins that are related to the aminoacylase subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.
Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the aminoacylase subfamily.
The present invention has a substantial similarity to aminoacylase-1. Aminoacylase-1 (ACY1, EC 3.5.1.14), a new type of metalloprotein, is a cytosolic enzyme with a wide range of tissue expression and has been postulated to function in the catabolism and salvage of acylated amino acids. ACY-1 is more highly expressed in kidney than in liver. ACY1 has been assigned to chromosome 3p21, a region reduced to homozygosity in small-cell lung cancer and renal cell carcinoma, and shows a reduced or absent expression in small-cell lung cancer cell lines and tumors. For a review related to aminoacylase-1, see Miller et al., Genomics 1990 September;8(1):149-54, Mitta et al., J Biochem (Tokyo) 1992 December;112(6):737-42.
Enzyme proteins, particularly members of the aminoacylase subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the aminoacylase subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.
The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the aminoacylase subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, T cells from T cell leukemia, ovary, brain, lung and leukocyte.